Twenty five year follow-up for breast cancer incidence and mortality of the Canadian national breast screening study: randomised screening trial

Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Abstract Objective: To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening. Design: Follow-up of randomised screening trial by centre coordinators, the study’s central office, and linkage to cancer registries and vital statistics databases. Setting: 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia). Participants: 89 835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography). Interventions: Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community. Main outcome measure: Deaths from breast cancer. Results: During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis. Conclusion: Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial

Microcarrier expansion of c-MycERTAM - modified human olfactory mucosa cells for neural regeneration

Human olfactory mucosa cells (hOMCs) have potential as a regenerative therapy for spinal cord injury. In our earlier work, we derived PA5 cells, a polyclonal population that retains functional attributes of primary human OMCs. Microcarrier suspension culture is an alternative to planar two-dimensinal culture to produce cells in quantities that can meet the needs of clinical development. This study aimed to screen the effects of 10 microcarriers on PA5 hOMCs yield and phenotype. Studies performed in well plates led to a 2.9-fold higher cell yield on plastic compared to plastic plus microcarriers with upregulation of neural markers β-III tubulin and nestin for both conditions. Microcarrier suspension culture resulted in concentrations of 1.4 × 10 5 cells/ml and 4.9 × 10 4 cells/ml for plastic and plastic plus, respectively, after 7 days. p75 NTR transcript was significantly upregulated for PA5 hOMCs grown on Plastic Plus compared to Plastic. Furthermore, coculture of PA5 hOMCs grown on Plastic Plus with a neuronal cell line (NG108-15) led to increased neurite outgrowth. This study shows successful expansion of PA5 cells using suspension culture on microcarriers, and it reveals competing effects of microcarriers on cell expansion versus functional attributes, showing that designing scalable bioprocesses should not only be driven by cell yields

Intracellular soluble α-synuclein oligomers reduce pyramidal cell excitability

The presynaptic protein α-synuclein (αSyn) aggregates during Parkinson's disease (PD) to form large proteinaceous amyloid plaques, the spread of which throughout the brain clinically defines the severity of the disease. During early stages of aggregation, αSyn forms soluble annular oligomers that show greater toxicity than much larger fibrils. These oligomers produce toxicity via a number of possible mechanisms, including the production of pore-forming complexes that permeabilize membranes. In the present study, two well-defined species of soluble αSyn oligomers were produced by different protocols: by polymerization of monomer and by sonication of fibrils. The two oligomeric species produced were morphologically similar, with both having an annular structure and consisting of approximately the same number of monomer subunits, although they differed in their secondary structure. Oligomeric and monomeric αSyn were injected directly into the soma of pyramidal neurons in mouse neocortical brain slices during whole-cell patch clamp recording. Using a combined experimental and modelling approach, neuronal parameters were extracted to measure, for the first time in the neocortex, specific changes in neuronal electrophysiology. Both species of oligomer had similar effects: (i) a significant reduction in input resistance and the membrane time constant and (ii) an increase in the current required to trigger an action potential with a resultant reduction in the firing rate. Differences in oligomer secondary structure appeared to produce only subtle differences in the activity of the oligomers. Monomeric αSyn had no effect on neuronal parameters, even at high concentrations. The oligomer-induced fall in neuronal excitability has the potential to impact both network activity and cognitive processing

Functional Outcomes of Thoracolumbar Junction Spine Fractures

Introduction. Few studies have evaluated the functionaloutcomes of traumatic thoracic and lumbar vertebral bodyfractures. This study evaluated the functional and clinicaloutcomes of patients, who sustained a fracture to thethoracolumbar area of the spine (T10 to L2 region), with≥ 25° kyphosis versus those with less kyphotic curvature. Methods. The trauma registry records of two level 1 traumacenters using ICD-9 codes for fracture to the thoracolumbarjuncture (T10 to L2 region) were reviewed. Kyphosis anglewas measured on the standing lateral thoracolumbar (T1 -L5) radiograph at initial trauma and at clinical follow-up.Functional outcome questionnaires, including the OswestryDisability Questionnaire (ODQ), the Roland Morris DisabilityQuestionnaire (RMDQ), and the Nottingham Health Profile(NHP), were evaluated at clinical follow-up. Work statusand medication used after trauma also were recorded. Results. A total of 38 patients met the inclusive criteria. Seventeenpatients (45%) had ≥ 25° kyphosis and 21 patients (55%)had < 25° kyphosis at follow-up. These two groups were similarbased on sex and age. Based on the ODQ Score, the RMDQScore, and the NHP, no statistically significant differenceswere detected between the two groups in regards to energy,pain, mobility, emotional reaction, social isolation, and sleep. Conclusions. Patients who sustained a fracture to the thoracolumbararea of the spine with ≥ 25° kyphosis do notreport worse clinical outcomes. When using the kyphosisangle as an indication for surgery, it should be used withcaution and not exclusively. KS J Med 2017;10(2):30-34

Developing pedagogies that work for Pre-Service and Early Career Teachers to reduce the Attainment Gap in Literacy, Numeracy and Health and Wellbeing. Research Question 3: What other practice or research might assist us in our purpose?

This report contributes to the Scottish Council of Deans of Education project related to the Scottish Attainment Challenge. It presents a literature review that responds to the third research question of the SCDE collaborative project: What other practice or research might assist us in our purpose? The purpose of this phase was to resource professional conversations and thinking in the teacher education sector, and to inform the final trial phase of the project. A literature search was undertaken using a range of strategies, to identify published accounts of innovative work from beyond Scotland in the following fields: initial teacher education for high poverty settings; pedagogies in literacy, numeracy and health and wellbeing; mentoring and induction. Each group of studies is summarised under themes with their potential for the SAC, ITE programmes and professional learning noted

Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice

Background Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO) mice. Methods 3T3-L1 mouse adipocytes were treated with Leucine (0.5 mM), β-hydroxy-β-methyl butyrate (HMB) (5 μM) or Resveratrol (200 nM) alone or in combination. In addition, diet-induced obese mice were treated for 6-weeks with low (2 g/kg diet) or high (10 g/kg diet) dose HMB, Leucine (24 g/kg diet; 200% of normal level) or low (12.5 mg/kg diet) or high (225 mg/kg diet) dose resveratrol, alone or as combination with leucine-resveratrol or HMB-resveratrol. Results Fatty acid oxidation, AMPK, Sirt1 and Sirt3 activity in 3T3-L1 adipocytes and in muscle cells, were significantly increased by the combinations compared to the individual treatments. Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT), insulin sensitivity (HOMAIR), improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin) and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect. Conclusion These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more practical dosing of resveratrol in the management of obesity, insulin-resistance and diabetes

Granitoid zircon forms the nucleus for minerals precipitated by carbonatite-derived metasomatic fluids at Chilwa Island, Malawi

This is the author's accepted manuscriptThe final version is available from Elsevier via the DOI in this recordMineralogical assemblages are fundamental to the interpretation of geological processes. Zircon is an integral petrographic component of the mineral assemblages present in fenites (rocks formed by alkaline metasomatism) associated with the 136 Ma-aged Chilwa Island carbonatite complex, Malawi. Zircon exhibits contrasting characteristics and properties across the fenite aureole that surrounds the carbonatite stock. It shows intense grain dissolution and subsequent replacement by pyrochlore in the more intensely metasomatised ‘high-grade’ fenite of the innermost part of the aureole. By contrast, relict zircon crystals form the nucleus for the development of apatite-ilmenite-REE mineral assemblages in less altered zones. These changes in zircon properties are considered to be evidence of the diverse nature of fluids that metasomatised the Chilwa Islands fenite aureole. Although zircon is a principal component of the fenite mineral assemblages, when dated by LA-ICP-MS techniques it was found to predate the other minerals present in the mineral assemblages and thus, the age of carbonatite intrusion, by over 380 Ma. Instead of co-crystallising with the assemblage, zircon is therefore interpreted as providing a focus around which the minerals in the fenite assemblage formed. This implies that caution is needed both in the interpretation of Zr mobility in metasomatic assemblages, and also in attributing a zircon age to the assemblage as a whole in such sequences

Associations between incident breast cancer and ambient concentrations of nitrogen dioxide from a national land use regression model in the Canadian National Breast Screening Study

Background: Air pollution has been classified as a human carcinogen based largely on epidemiological studies of lung cancer. Recent research suggests that exposure to ambient air pollution increases the risk of female breast cancer especially in premenopausal women. Methods: Our objective was to determine the association between residential exposure to ambient nitrogen dioxide (NO2) and newly diagnosed cases of invasive breast cancer in a cohort of 89,247 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985.

Towards an organizational folklore of policing: the storied nature of policing and the police use of storytelling.

For police officers, much of the working day consists of telling stories about everyday policing and events. Although the study of narrative and storytelling in organizational contexts is an expanding area of research, the same cannot be said of the study of narrative and storytelling in a police context, which remains an under-researched, although not unexplored, subject of study. Using the work of management-narrative theorists such as David Boje and Yiannis Gabriel as a starting point, this article considers policing organizations and agencies as storytelling organizations. This is achieved through a literature review of the 'storied' nature of policing and the police use of storytelling in an organizational context. Thus, this reflective article contributes to the developing literature in the field by reviewing and mapping the literature, highlighting potential areas for future research